Dept of Neuroscience, Canadian Centre for Behavioural Neuroscience, The University of Lethbridge, Lethbridge, Canada.Center for the Neurobiology of Learning and Memory, University of California at Irvine, Irvine, CA

Abstract

Decades of research identify the hippocampal formation as central to memory storage and recall. Events are stored via distributed population codes, whose parameters (e.g., sparsity and overlap) determine both storage capacity and fidelity. However, it remains unclear whether the parameters governing information storage are similar between species. Because episodic memories are rooted in the space in which they are experienced, the hippocampal response to navigation is often used as a proxy to study memory. Critically, recent studies in rodents that mimic the conditions typical of navigation studies in humans and nonhuman primates (i.e., virtual reality) show that reduced sensory input alters hippocampal representations of space. The goal of this study was to quantify this effect and determine whether there are commonalities in information storage across species. Using functional molecular imaging, we observe that navigation in virtual environments elicits activity in fewer CA1 neurons relative to real-world conditions. On the other hand, comparable neuronal activity is observed in hippocampus region CA3 and the dentate gyrus under both conditions. Surprisingly, we also find evidence that the absolute number of neurons used to represent an experience is relatively stable between nonhuman primates and rodents. We propose that this convergence reflects an optimal ensemble size for episodic memories.

Significance Statement

One primary factor constraining memory capacity is the sparsity of the engram — the proportion of neurons that encode a single experience. Investigating sparsity in humans is hampered by lack of single cell resolution and differences in behavioral protocols. Sparsity can be quantified in freely-moving rodents, but extrapolating these data to humans assumes that information storage is comparable across species and is robust to restraint-induced reduction in sensory input. Here we test these assumptions, and show that species differences in brain size build memory capacity without altering the structure of the data being stored. Furthermore, sparsity in most of the hippocampus is resilient to reduced sensory information. This information is vital to integrating animal data with human imaging navigation studies.

Footnotes

Now at National Institute of Mental Health. This article was prepared while Dr. Lisanby was employed at Duke University. The opinions expressed in this article are the author's own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.

The authors declare no competing financial interests.

This work was supported by NIH Grant R01 AG003376, McKnight Brain Research Foundation (CAB), the Natural Sciences and Engineering Research Council of Canada Grants (DFM and BLM), NIH Grant MH060884 (SHL) and Alberta Innovates Health Solution Polaris award (BLM). We thank Tom Beach for surgical assistance; David Towers, and Michael Montgomery for technical assistance; Luann Snyder and Michelle Carroll for administrative assistance.